Container for medicament powder

ABSTRACT

There is provided a container for a medicament powder formed from a material comprising a desiccant. In one embodiment the container is a medicament dispenser comprising a body defining a reservoir for medicament in powder form, and an outlet in communication with said reservoir. In another embodiment the container is a medicament dispenser comprising a body defining a chamber for receipt of a medicament carrier, and an outlet in communication with said chamber. Methods of controlling moisture flow are also described.

TECHNICAL FIELD

[0001] The present invention relates to containers and dispensers formedicament powders. In particular, the invention relates to dry powderinhalation dispensers and components thereof which substantiallyalleviate or reduce moisture build-up therein. The invention alsorelates to a method for reducing moisture ingress inside a dry powderinhaler.

BACKGROUND TO THE INVENTION

[0002] Medicaments for treating respiratory disorders are frequentlyadministered as dry powder formulations through the mouth and nose. Drypowder medicament dispensers, such as inhalers, are used in theadministration of these drugs, inhalation by the patient resulting inuptake of a specified dosage of medicament through the nose or mouth.The drug may be stored as a dry powder within a reservoir in the body ofthe inhaler, a metering chamber being utilised to administer a specifieddose of medicament. Alternatively, more sophisticated medicamentdispensers employ medicament carriers, such as individual capsules orblister packs/strips containing defined doses of powdered drug.

[0003] Patients often rely on medication delivered by dry powderinhalers for rapid treatment of respiratory disorders that aredebilitating and in some cases life threatening. It is, therefore,essential that the prescribed dose of drug is delivered accurately andconsistently to meet the patient's needs and comply with therequirements of regulatory authorities.

[0004] A problem which can occur in the storage and product lifetime ofan inhaler is ingress of moisture into the medicament powder. A build-upof moisture can prevent the administration of an effective dose ofmedicament by causing an increase in particle size and/or adherence ofhygroscopic particles to the walls of the carrier or device, therebyleading to reduced uptake via inhalation by the patient. In extremecases, depending upon the chemical nature of the medicament, moisturebuild-up may lead to degradation of the drug.

[0005] Another problem can be microbial contamination, which is oftenassisted by the undesirable presence of excess moisture.

[0006] The Applicants have found that the inclusion of a desiccant inthe body of the inhaler or the walls of the medicament carrier cansignificantly improve the aforementioned problems. Furthermore, storageof the inhaler or medicament carrier within a sealed is packageincorporating a desiccant, can markedly reduce moisture ingress.

[0007] The Applicants has also found that the aforementioned problemscan be ameliorated by controlling the ingress of moisture to, or egressof moisture from, the medicament container. Control may be achieved byeither suitable choice of container materials or by enclosure of thecontainer or a dispenser including the container in a suitable package.The control need not absolutely prevent moisture transfer. Indeed, theApplicants have found that under certain conditions a limited degree ofmoisture transfer can be desirable.

[0008] WO 99/32180 teaches the inclusion of moisture permeable chamberscontaining desiccants within a blister pack. U.S. Pat. No. 5,740,793discloses the inclusion of a desiccant cartridge within an inhaler orthe medicament carrier cassette. U.S. Pat. No. 5,394,868 describes achamber within a powder inhaler for holding a desiccating substance. Theuse of desiccant filters within medicament dispensers is described inU.S. Pat. Nos. 5,687,746 and 5,775,320, and PCT patent application no.WO 89/01348.

SUMMARY OF INVENTION

[0009] According to the present invention, there is provided a containerfor a medicament powder formed from a material comprising a desiccant.

[0010] In one aspect, the container is suitable for containing ameasured dose of medicament. Packs in blister pack form for thecontainment of a unit dose medicaments are envisaged, as are packscontaining multiple unit dose blisters arranged sequentially orotherwise, such as in series form. A particular multi-unit dosearrangement comprises an elongate strip having multiple blistersarranged in series thereon.

[0011] In another aspect, the container is a reservoir for dry powdermedicament. Metering means are provided to enable metering of dose fromthe reservoir and transport of that dose to a delivery position.

[0012] In one aspect, the container is a medicament dispenser comprisinga body defining a reservoir for medicament in powder form, and an outletin communication with said reservoir for release of the medicament. Inone aspect, the device is an inhaler and the outlet is one through whicha user can inhale.

[0013] In another aspect, the container is in the form of a reloadablecartridge comprising a medicament pack (e.g. in multi-unit dose blisterform or reservoir form). The cartridge is shaped and sized for receiptby a medicament delivery device (e.g. an inhaler device).

[0014] In another aspect, the container is a medicament dispensercomprising a body defining a chamber for receipt of a medicamentcarrier, and an outlet in communication with said chamber for release ofthe medicament. In one aspect, the device is an inhaler and the outletis one through which the user can inhale.

[0015] In yet another aspect, the body consists of the materialcomprising the desiccant.

[0016] In one aspect, the body comprises the material comprising thedesiccant.

[0017] In another aspect, the material comprising the desiccant coatsthe body e.g. part or whole of the inside of the body.

[0018] In yet another aspect, the material comprising the desiccant isimpregnated throughout the body.

[0019] In one aspect, the material comprising the desiccant lines thebody (e.g. the interior of the body which contacts the medicament powderin use).

[0020] Optionally the desiccant comprising material may be locatedaround a seal for sealing the reservoir or medicament carrier optionallythe seal (e.g. in the form of a sealing ring) may itself comprise orconsist of a desiccant.

[0021] In another aspect, the container is a medicament carrier.

[0022] In yet another aspect, the medicament carrier is a capsulecomprising a wall enclosing the medicament.

[0023] In one aspect, the medicament carrier is a blister packcomprising a base sheet and a lid.

[0024] In another aspect, the medicament carrier comprises a materialcomprising a desiccant.

[0025] In yet another aspect, the material comprising the desiccantcoats the wall, or the base sheet, or the lid of the medicament carrier.

[0026] In one aspect, the material comprising the desiccant impregnatesthe wall, or base sheet, or lid of the medicament carrier.

[0027] In another aspect, the material comprising the desiccant linesthe wall, or base sheet, or lid of the medicament carrier.

[0028] In another aspect, the material comprising the desiccant ismoulded into the wall, or base sheet, or lid of the medicament carrier.

[0029] In yet another aspect, a well containing desiccant surroundsindividual pockets in the blister packs.

[0030] In one aspect, the blister pack comprises a laminate comprising adesiccant. Suitably, the laminate comprises material selected from thegroup consisting of metal foil, organic polymeric material and paper.Suitable metal foils include aluminium or tin foil having a thickness offrom 5 to 100 μm, preferably from 10 to 50 μm, such as 20 to 30 μm.Suitable organic polymeric materials include polyethylene,polypropylene, polyvinyl chloride and polyethylene terephthalate.

[0031] Suitably, the base sheet and lid comprise different materials.

[0032] In another aspect, the material comprising the desiccant is anorganic polymeric plastic having particular characteristics e.g. athermoplastic.

[0033] In yet another aspect, the organic polymeric plastic is apolyamide.

[0034] Preferably the desiccant is selected from the group consisting ofsilica gel, zeolite, alumina, bauxite, anhydrous calcium sulphate,activated bentonite clay, water-absorbing clay, molecular sieve and anymixtures thereof.

[0035] In one aspect, the container additionally comprises a medicamentin dry powder form. Suitably, the medicament is suitable for thetreatment of respiratory disorders. Preferably, the medicament issalmeterol xinafoate, fluticasone propionate or a combination thereof.

[0036] In another aspect of the present invention there is provided amethod of reducing water ingress into a medicament powder comprisingusing a container for a medicament powder according to any of thepreceding claims.

[0037] In another aspect of the present invention there is provided apackage for storage of a container for a medicament powder formed from amaterial capable of controlling the ingress of moisture thereto oregress or moisture therefrom.

[0038] In one aspect, the material is impermeable to moisture.

[0039] In another aspect, the material controls the ingress or egress ofmoisture such that the ambient moisture content within the package isessentially constant, such as varying by no more than ±20%, preferablyby less than ±10%. Ambient moisture content may for example be measuredby Relative Humidity within the package. The preferred absolute level ofmoisture content will vary from medicament to medicament but may bereadily determined through laboratory testing.

[0040] In another aspect, the material enables moisture transfer in oneway only i.e. ingress only or egress only.

[0041] In another aspect, the material enables moisture transfer toeither a set minimum/maximum moisture content within the package orwithin a set minimum/maximum moisture transfer rate.

[0042] In another aspect, the material is also capable of controllingthe flow of other gaseous or vapour form species. Tyvek (trade name) isa suitable material.

[0043] In one aspect, the package is wrappable and sealable around thecontainer to form an enclosed volume in which the container is disposed,the package being impermeable to water vapour, thereby substantiallyreducing ingress of water vapour and particulate matter into saidenclosed volume.

[0044] In another aspect, the package additionally comprises a desiccantwithin the enclosed volume.

[0045] Preferably the desiccant is selected from the group consisting ofsilica gel, zeolite, alumina, bauxite, anhydrous calcium sulphate,activated bentonite clay, water-absorbing clay, molecular sieve and anymixtures thereof.

[0046] In one aspect the package includes at least one heat sealablelayer and at least one layer of a metal foil.

[0047] In another aspect, the metal comprising said metal foil isselected from the group consisting of aluminium, tin, iron, zinc andmagnesium.

[0048] In yet another aspect, the package includes protective layerslocated on the outside of the package.

[0049] In one aspect, the protective layer comprises a polyester filmand the heat sealable layer comprises an ionomer film.

[0050] In another aspect of the present invention there is provided amethod of storing a container for a medicament powder comprisingproviding a packaging material which is capable of controlling the flowof water vapour; filling a container with a medicament powder; wrappingsaid container with said package material to form an enclosed volume inwhich said container is disposed therein; and sealing the package.

[0051] In yet another aspect, the method additionally comprisesproviding a desiccant within the enclosed volume.

[0052] In one aspect, the sealing comprises heat sealing said packagingmaterial. In other aspects, the seal is formed by ultrasonic welding,heat stamping, adhesive or laser welding methods.

[0053] In another aspect of the present invention there is provided apackaged container, comprising a container containing a medicamentpowder; and an overwrap package enclosing the container and a desiccant;wherein the container and the desiccant are sealable within theoverwrap. Preferably the overwrap comprises a desiccant material and/oris lined, coated or impregnated with a desiccant material.

[0054] The overwrap package may be in the form of a shrink wrap or of aloose wrap e.g. in sachet form. Any spare volume within the overwrap maybe evacuated or an inert gas such as nitrogen deliberately inserted.

[0055] In another aspect of the present invention there is provided apackaged powder medicament dispenser (or reloadable cartridge thereforas described supra) comprising a medicament dispenser for a medicamentpowder; and an overwrap package enclosing the medicament dispenser,wherein the medicament dispenser are sealable within the overwrap. Theoverwrap package may comprise desiccant, and or the package may havedesiccant contained therewithin. The medicament dispenser may comprise apowder reservoir or a medicament carrier for containment of medicament.

[0056] Where the overwrap comprises desiccant it may be impregnated orotherwise blended with material or added as a coating or a liner.

[0057] In another aspect, the body of said medicament dispenser alsocomprises a desiccant.

[0058] Preferably the desiccant is selected from the group consisting ofsilica gel, zeolite, alumina, bauxite, anhydrous calcium sulphate,activated bentonite clay, water-absorbing clay, molecular sieve, zincchloride, and any mixtures thereof.

[0059] In another aspect of the present invention there is provided acontainer for a medicament powder formed from a material capable ofcontrolling the ingress of moisture thereto or egress or moisturetherefrom.

[0060] In one aspect, the material is impermeable to moisture.

[0061] In another aspect, the material controls the ingress or egress ofmoisture such that the ambient moisture content within the package isessentially constant, such as varying by no more than ±20%, preferablyby less than ±10%.

[0062] In another aspect, the material enables moisture transfer in oneway only i.e. ingress only or egress only.

[0063] In another aspect, the material enables moisture transfer toeither a set minimum /maximum moisture content within the package orwithin a set minimum/maximum moisture transfer rate.

[0064] In another aspect, the material is also capable of controllingthe flow of other gaseous or vapour form species.

[0065] In other aspects, the medicament container or overwrap thereforor any part of a medicament dispenser for use therewith is comprised ofa material having desiccant blended or otherwise loaded or impregnatedtherein. Suitable materials are described in PCT Application Nos.WO99/62697 and WO/00/17258 in the name of Capitol Speciality PlasticsInc.

[0066] Suitable materials comprise a thermoplastic/desiccant blend.Examples of thermoplastics include polyolefin, polyethylene,polycarbonate, polyamide, ethylenevinyl acetate copolymer,ethylene-methacrylate copolymer, polyvinyl chloride, polystyrene,polyester, polyester amide, polyacrylic ester, and polyvinylidenechloride, acrylic, polyurethane, polyacetal, and polycarbonate. Theseand other thermoplastics may be utilized either singularly, or incombinations.

[0067] The concentration of desiccant entrained (e.g. mixed or blended)within the thermoplastic may exceed seventy-five percent (75%) to notgreater than eighty percent (80%) by weight, so that about seventy-fivepercent (75%) may extend to eighty percent (80%) by weight. Typically,however, the desiccant concentration will fall within a range of fortyto seventy-five percent (40-75%) desiccant to thermoplastic, by weight.This concentration is considered to be a high concentration for mostthermoplastics. The maximum desiccant bearable concentrations will varyamong the various types of thermoplastics due to their differingcharacteristics. In the instance of polyethylene or polypropylene, forexample, the maximum concentration of desiccant will be aboutseventy-five percent (75%) by weight. As the desiccant concentrationswithin the thermoplastics increase, the performance of the materialdegenerates to unacceptable levels. At lower levels of desiccantconcentrations, about forty percent (40%) could extend to as low asthirty percent (30%) where the limits of a viable product are reached.

BRIEF DESCRIPTION OF INVENTION

[0068]FIG. 1 shows a medicament carrier in the form of a capsuleaccording to the present invention.

[0069]FIG. 2a is a cross-sectional side elevation of a single medicamentblister strip impregnated with a desiccant according to the presentinvention.

[0070]FIG. 2b is a top perspective of a medicament blister stripillustrated in FIG. 2a.

[0071]FIG. 3a is a cross-sectional side elevation of a single medicamentblister having a laminate comprising a desiccant according to thepresent invention.

[0072]FIG. 3b is a top perspective of a medicament blister stripillustrated in FIG. 3a.

[0073]FIG. 4a is a cross-sectional side elevation of a single medicamentblister having a ring containing a desiccant impregnated into thelaminate surrounding the blister pocket.

[0074]FIG. 4b is a top perspective of the medicament blister shown inFIG. 4a.

[0075]FIG. 5 shows a cross-sectional dry powder inhaler comprising apowder reservoir according the present invention.

[0076]FIG. 6 shows a cross-sectional dry powder inhaler comprising amedicament carrier according to the present invention.

[0077]FIG. 7 is a top perspective of a package for storing a dry powderinhaler according to the present invention.

[0078]FIG. 8 is a side perspective of the package of FIG. 7.

[0079]FIG. 9 is a cut-away bottom perspective of the package for storinga dry powder inhaler according to the present invention.

[0080]FIG. 10 is a cross-sectional view of the package for storing a drypowder inhaler according to the present invention.

DETAILED DESCRIPTION OF THE DRAWINGS

[0081] The medicament carrier in FIG. 1 is in the form of a capsule 1comprising a wall 2 enclosing medicament powder 5. The wall 2 comprisesa desiccant 3 which reduces or otherwise controls moisture ingress intothe capsule 1 during storage and/or when in situ within the body of theinhaler (not shown). Medicament powder 5 is released on piercing thewall 2 of capsule 1 and may be inhaled by a patient.

[0082]FIG. 2a shows a sectional side-elevation of a single blister strip106 comprising a pocket 107, containing dry powder 105, base 110 and lidcomprising laminates 114, 115. The lid is composed of a metallic foillaminate 114 bound to a plastic laminate 115. In the diagram, the lid114, 115 is hermetically sealed to base 110 by appropriate means (e.g.adhesion, welding). Base 110 comprises an organic polymeric plasticimpregnated with desiccant 103. In use, the desiccant absorbs anymoisture which permeates through the lid 114, 115 and base 110,maintaining the powder 105 in a dry condition until the lid 114, 115 isremoved from the base 110.

[0083] A top perspective of the blister strip 106 showing pockets 107 isillustrated in FIG. 2b. Laminated lid 114, 115 is sealed to base 110which is impregnated with desiccant 103.

[0084]FIG. 3a shows a cross-sectional elevation of a different singleblister strip 206 according to the invention. The blister strip 206 iscomposed of several laminated sheets, the lid being formed from metallicfoil 214 and plastic laminate 215 while the base comprises plasticlaminates 210 and 211. The plastic laminate 211 comprises a desiccantmaterial 203 for absorbing any moisture which permeates throughlaminated sheets 214, 215 and 210, thereby reducing ingress intomedicament powder 205 within pocket 207.

[0085]FIG. 3b is a top perspective of a blister strip 206 showingseveral blisters as described in FIG. 3a. Metallic foil 214 and plasticlaminate 215 form a lid which is hermetically sealed, by appropriateadhesive or welding means, to the base of strip 206. The base comprisesplastic laminates 210 and 211, laminate 211 being disposed on theinternal surface of pocket 207 and comprising a desiccant.

[0086]FIG. 4a shows a cross-sectional elevation of yet another singleblister strip 306 according to the invention. Metallic foil 314 andplastic laminate 315 form a lid for base 310 which are hermeticallysealed together to reduce moisture ingress into pocket 307 containingmedicament powder 305. The circumference of pocket 307 is surrounded bya ring 319, within base 310, comprising desiccant 303 which absorbsmoisture which permeates into the blister, particularly between lidsheet 315 and base sheet 310.

[0087] A plan perspective of the single blister strip 314 shown in FIG.4a is illustrated in FIG. 4b. The ring 319 of material comprisingdesiccant 303 surrounds pocket 307 thereby absorbing any moisture whichpermeates into the pocket 307 through foil 314 and laminates 315 and/orbase sheet 310, together with moisture ingress between lid and basesheets 315, 310.

[0088]FIG. 5 shows a sectional view of a dry powder inhaler 420according to the present invention. The inhaler 420 comprises a body 421which defines a reservoir 423 and a reservoir cover 424. The reservoircontains a supply of medicament in dry powder form 405. The walls 423 ofthe reservoir, defined by the body 421, are comprised of a desiccantmaterial 403. Base 425 and body 421 define an aperture 430 through whichpowder 405 can pass from the reservoir to the dosing member 432. Powder405 is guided by the walls 423 of the reservoir, which form a hopper, tothe dosing member 432. Extending laterally from the lower end of themain body 421 is mouthpiece 435, through which the patient inhales viapassage 433. If the device were intended for nasal inhalation this wouldbe replaced by a nosepiece. The desiccant material 403, comprising walls423, reduce moisture absorption by medicament powder 405. Optionally adesiccant comprising material may be located within the walls of passage433 and/or a ring of same material around the metering valve (not shown)which controls the flow of medicament into passage 433.

[0089]FIG. 6 shows a simplified cross-sectional plan view of a drypowder inhaler comprising a medicament carrier according to the presentinvention. The inhaler 540 dispenses unit doses of medicament powderfrom a medicament blister strip 506. The inhaler is comprised of anouter casing 544 enclosing a medicament strip 506 within body 521. Themedicament strip may be, for example, any of those described in FIGS. 2ato 4 b above. The internal walls of body 521 are comprised of adesiccant material (not shown) which reduce the levels of moisturewithin the internal cavity of the inhaler, thereby protecting themedicament powder within strip 506. The patient uses the inhaler byholding the device to his mouth, depressing lever 538, and inhalingthrough mouthpiece 535. Depression of lever 538 activates the internalmechanism of the inhaler, such that the lid 514 and base 510 sheets ofcoiled medicament blister strip 506 are separated at index wheel 541 byuse of contracting wheel 542 and base wheel 543. A unit dose of powderedmedicament within blister pocket 507 is released and may be inhaled bythe patient through exit port 533 and mouthpiece 535.

[0090]FIG. 7 shows a top perspective of a container storage system forstoring a dry powder inhaler or cartridge refill therefor according tothe present invention. The container storage system 650 includes apackage or wrapping 652 that employs multi-layers of material 970, 972,974. (See FIG. 10.) The package 652 further includes fin seams 654, 656which are disposed along two parallel side edges of the package andalong a single longitudinal edge of the package 652. The package 652comprises a desiccant material, or alternatively is lined, coated orimpregnated with a desiccant material.

[0091] The number and type of fin seams 654, 656 are not limited to thetypes shown in the drawings. The package 652 can include additionalseams or significantly fewer seams such as a continuous single seam. Theorientation of the seams 654, 656 is not limited to the orientationshown in the drawings. The orientation of the seams 654, 656 istypically a function of the sealing device and such seams may beoriented in a manner which substantially increases manufacturingefficiency. During manufacture, the longitudinal seam 654 may be formedfirst by heat sealing and the two end seams 656 may then be formed byheat sealing to close the package. Other types of seams include, but arenot limited to, gusset type seams which include excess material whichprovides expansibility, stitched type seams, or mechanically crimpedseams, and other like structures.

[0092] The container storage system includes a dry powder inhaler 820(see FIG. 9). While the preferred inhaler is a dry powder inhaler 820,other dry powder inhalers (such as that described in FIG. 6) are notbeyond the scope of the present invention.

[0093]FIG. 8 shows a side perspective of the container storage system ofFIG. 7. The fin seams 654 and 656 in FIG. 7 are formed by a conventionalheat sealing device which mechanically crimps sides of the package 750together while simultaneously providing heat to the sides 654, 656/756(FIGS. 7 and 8). The heat sealing device typically has electrical heaterelements shaped to produce the pattern of the fin seams 654, 656/756where the fin seams include multiple ridges 658/758. The sealingmechanism of the container storage system 650/750 of the presentinvention is not limited to heat sealing devices. Other sealing devicesinclude, but are not limited to, glue sealing machines, sonic weldingmachines, electron beam radiation machines, and other like sealingdevices.

[0094] As shown in FIG. 7, the package 750 preferably has asubstantially rectangular configuration with a substantially ellipticalcross section, however, other shapes of the package 750 are not beyondthe scope of the present invention. Other shapes include, but are notlimited to circular, square, triangular, trapezoidal, pentagonal,hexagonal, octagonal, and other like shapes. The shape of the package750 is preferably a function of the shape of the enclosed medicamentpowder container 34 as well as the amount and type of storage spacesince the package 752 is made from flexible materials as will bedescribed in further detail below.

[0095]FIG. 9 shows a cut-away bottom perspective of the package forstoring a dry powder inhaler according to the present invention. Thepackage 852 provides an enclosed volume 860 in which the inhaler 820 isdisposed therein. The size of the enclosed volume 860 can be adjustedaccording to the size of the inhaler 820 and related parts thereto.Preferably, the enclosed volume 860 is of a size which permits relativeease of closing respective sides and layers 852, 26 and 28 withoutsubstantial stretching of the package 852. The enclosed volume 860 maybe substantially evacuated prior to formation of the fin seams 858, 854(not shown) to substantially reduce any water vapour being present inthe enclosed volume 860. The enclosed volume 860 may be evacuated tosuch a degree that the enclosed volume 860 is a vacuum region around themedicament inhaler 820. While the enclosed volume 860, may remainconstant, its relative shape may change according to shifting of theinhaler 820 disposed within the enclosed volume 860. In a preferredembodiment, a porous container of moisture absorbing material 862 laysadjacent to the mouthpiece 835 in a loose or free flowing manner.Alternatively, the moisture absorbing material 862 can be secured to theinside of the flexible package. In another alternative embodiment, themoisture absorbing container 862 may be attached to a bracket structuresuch as a ring which is fastened to the inhaler 820.

[0096] In one possible embodiment, the moisture absorbing material maybe attached to the external surface of the mouthpiece 835 by a fasteningdevice such as a rubber band 863. The fastening device 863 is preferablya removable elastic mechanism such as a rubber band. However, otherfastening devices are not beyond the scope of the present invention.Other fastening devices include, but are not limited to, adhesives,adhesive tapes, shrink-wrap plastic, fasteners such as screws, nails, orrivets, compartments which are part of the mouthpiece housing 46, andother like attachment devices. In an alternative embodiment (not shown),a plurality of beads of material comprising a desiccant may be placedwithin the enclosed space 860. Similarly, other carriers comprised of adesiccant material may be enclosed within space 860 to absorb excessmoisture from the enclosure.

[0097]FIG. 10 is a cross-sectional view of the package for storing a drypowder inhaler according to the present invention. The amorphous shapeof the enclosed volume 960 is attributed to the flexible materials whichmake up the layers 970, 972, 974 of the package 952. The enclosed volume960 can be varied in size such that it substantially conforms to theshape of the inhaler and any related parts thereto or such that theenclosed volume 960 is larger than the inhaler 820, as shown in FIG. 9.When the enclosed volume is of a size which is substantially equivalentwith the surface area of the inhaler 820 and related parts, the layers970, 972, and 974 of material substantially conform to the shape of theinhaler and related parts. The package is preferably placed in aseparate, more rigid container, such as a paperboard or cardboard box(not shown) typically used in the pharmaceutical industry. The packagemay expand during storage due to slow leakage of volatiles from theplastics constituting the body of the inhaler. In this situation, theshape of the package may conform to some extent to the internal shape ofthe rigid container if the volume of the rigid container is justslightly larger than the expanded volume of the flexible package.

Flexible Packaging Materials

[0098] The flexible packaging material can be any material which isimpervious to or substantially impervious to moisture. The packagingmaterial is preferably permeable to volatiles which may escape from theplastics forming the body of the inhaler and/or the medicament carrier,by diffusion or otherwise, thereby preventing a build-up in pressure.

[0099] For ease of manufacturing, and in order to provide the necessaryproperties to the packaging material, the flexible packaging materialpreferably comprises a non-thermoplastic substrate (such as a metalfoil) and a heat sealable layer disposed thereon, and an additionalprotective layer, such as a polymer film of polyester. The heat sealablelayer is usually disposed on the inner surface of the assembled package.The additional protective layer is usually disposed on the surfaceopposite the heat sealable layer. An example of a particularly usefulfoil laminate is a polyester film adhesively laminated to aluminium foiladhesively laminated to Ionomer (SURLYN™) film, for example, 12μpolyester/9μ aluminum/50μ ionomer film supplied by Lawson Mardon Singen(LMS). To further reduce moisture ingress, thicker metal films, such as20 to 25μ, may be used.

[0100] The substrate is preferably formed from aluminium foil. However,other metals for the substrate include, but are not limited to, tin,iron, zinc, or magnesium formed on a sheet by vacuum deposition orsputtering and a carboxyl group-containing polyolefin layer formed onthe metal layer by lamination.

[0101] The heat sealable layer can be formed from any thermoplastic orthermosetting material such as an ionomer resin, polyolefin, orcycloolefin copolymer. Ionomer resins typically include ionicallycross-linked ethylene-methacrylic acid and ethylene acrylic acidcopolymers. Properties which distinguish these ionomers resins fromother polyolefin heat-sealed polymers are high clarity, high impactresistance, low haze in lamination, tear resistance, abrasionresistance, solid state toughness, and moisture imperviousness. In thepreferred embodiment, the heat sealable layer is made out of SURLYN™ (anionomer resin) or a form of polyethylene to provide sufficient heatsealing properties.

[0102] The outer protective layer, if present, can be formed of anymaterial as long as the final laminate has the requisite properties.

[0103] Preferably, the protective layer (e.g., polyester) is adhesivelylaminated to the substrate (e.g., aluminium) and the substrate layer inturn is adhesively laminated to the heat sealable layer (e.g., theionomer film or SURLYN™ (an ionomer resin)). Preferred exemplarythicknesses of the three layers include a protective layer 1 to 40,preferably 4 to 30, more preferably 10 to 23 microns, and mostpreferably 12 microns; a substrate layer of 1 to 100, preferably 3 to70, more preferably 5 to 50 microns, more preferably 6 to 20 microns,and most preferably 9 microns. For the heat sealable layer, preferredexemplary thicknesses include thicknesses of 1 to 100, preferably 5 to70, more preferably 10 to 60, more preferably 20 to 55 microns, and mostpreferably 50 microns.

[0104] Adhesives may be used to join the respective layers of materialstogether. The adhesive layers are typically substantially smaller inthickness relative to the thickness of the substrate, heat sealableand/or protective layers which they bond. The number, size, and shape ofthe layers are not limited to those layers shown in the drawings. Anynumber of layers with relative areas of any size and predeterminedthicknesses may be used so long as the flexible package forms anenclosed volume which substantially prevents ingression of water vapourand particulate matter into the enclosed volume while permittingegression out of the enclosed volume of any volatile released from theplastics used in the body of the inhaler or the medicament carrier. Thesize, shape, and number of layers of the package are typically afunction of the size and contents of the inhaler and/or medicamentcarrier.

[0105] The package is believed to operate similarly to a virtual one-wayvalve due to the composition of the layers and due to the transmissionrate of water vapour molecules into the enclosed volume relative to thetransmission rate of gas molecules of a plastic volatile, such asformaldehyde, out of the enclosed volume. The package permits thevolatile to diffuse out of the enclosed volume while substantiallypreventing water vapour and other particulate matter from entering theenclosed volume. Excess or leakage of the volatile is permitted toegress from the package. The virtual one-way valve function of thepackage prevents or minimizes the chance of any sudden ruptures orprevents or minimizes unexpected expulsion of the plastic volatileduring opening of the package.

Moisture Absorbing Materials

[0106] The moisture absorbing material is preferably a silica geldesiccant sachet. However, other vapour or moisture absorbing mechanismsare not beyond the scope of the present invention. Other vapour ormoisture absorbing materials include desiccants made from inorganicmaterials such a zeolites and aluminas. Such inorganic materials ofvapour or moisture absorbing materials have high water absorptioncapacities and favourable water absorption isotherm shapes. The waterabsorption capacity of such materials typically varies from 20 to 50weight percent. In the preferred embodiment, the absorbing material is aMlNIPAX™ supplied by Multisorb Technologies in the United States andSilgelac in Europe (silica gel packaged inside TYVEK®, which is a nylonmesh bonded with a microporous polyurethane). Other exemplary moistureabsorbing materials include, but are not limited to, alumina, bauxite,anhydrous, calcium sulphate, water-absorbing clay, activated bentoniteclay, a molecular sieve, or other like materials which optionallyinclude a moisture sensitive colour indicator such as cobalt chloride toindicate when the desiccant is no longer operable. While in thepreferred embodiment of the present invention, the package is designedto substantially prevent ingression of water vapour and particulatematter into the enclosed volume, the moisture absorbing material isplaced within the enclosed volume in order to absorb any residualmoisture present in the atmosphere or on the external surface of thepressurized container or mouthpiece or a combination thereof, prior tosealing the package.

[0107] The desiccant should be present in an amount sufficient to absorbany residual moisture inside the package. When silica gel is used, 1 gto 10 g of silica gel is sufficient for a typical dry powder inhaler.Moreover, the desiccant should be present in an amount sufficient toabsorb any moisture that possibly ingresses from the externalenvironment. It is also possible to place the desiccant inside thecontainer, either loose in the canister or as part of an assemblyattached to the canister.

Medicaments

[0108] Appropriate medicaments may thus be selected from, for example,analgesics, e.g., codeine, dihydromorphine, ergotamine, fentanyl ormorphine; anginal preparations, e.g., diltiazem; antiallergics, e.g.,cromoglycate (eg s the sodium salt), ketotifen or nedocromil (eg as thesodium salt); antiinfectives e.g., cephalosporins, penicillins,streptomycin, sulphonamides, tetracyclines and pentamidine;antihistamines, e.g., methapyrilene; anti-inflammatories, e.g.,beclomethasone (eg as the dipropionate ester), fluticasone (eg as thepropionate ester), flunisolide, budesonide, rofleponide, mometasone egas the furoate ester), ciclesonide, triamcinolone (eg as the acetonide)or 6α,9α-difluoro-11β-hydroxy-16α-methyl-3-oxo-17α-propionyloxy-androsta-1,4-diene-17β-carbothioicacid S-(2-oxo-tetrahydro-furan-3-yl) ester; antitussives, e.g.,noscapine; bronchodilators, e.g., albuterol (eg as free base orsulphate), salmeterol (eg as xinafoate), ephedrine, adrenaline,fenoterol (eg as hydrobromide), formoterol (eg as fumarate),isoprenaline, metaproterenol, phenylephrine, phenylpropanolamine,pirbuterol (eg as acetate), reproterol (eg as hydrochloride), rimiterol,terbutaline (eg as sulphate), isoetharine, tulobuterol or4-hydroxy-7-[2-[[2-[[3-(2-phenylethoxy)propyl]sulfonyl]ethyl]amino]ethyl-2(3H)-benzothiazolone;adenosine 2a agonists, eg2R,3R,4S,5R)-2-[6-Amino-2-(1S-hydroxymethyl-2-phenyl-ethylamino)-purin-9-yl]-5-(2-ethyl-2H-tetrazol-5-yl)-tetrahydro-furan-3,4-diol(e.g. as maleate); α₄ integrin inhibitors eg(2S)-3-[4-({[4-(aminocarbonyl)-1-piperidinyl]carbonyl}oxy)phenyl]-2-[((2S)-4-methyl-2-{[2-(2-methylphenoxy)acetyl]amino}pentanoyl)amino]propanoicacid (e.g as free acid or potassium salt), diuretics, e.g., amiloride;anticholinergics, e.g., ipratropium (eg as bromide), tiotropium,atropine or oxitropium; hormones, e.g., cortisone, hydrocortisone orprednisolone; xanthines, e.g., aminophylline, choline theophyllinate,lysine theophyllinate or theophylline; therapeutic proteins andpeptides, e.g., insulin or glucagon; vaccines, diagnostics, and genetherapies. It will be clear to a person skilled in the art that, whereappropriate, the medicaments may be used in the form of salts, (e.g., asalkali metal or amine salts or as acid addition salts) or as esters(e.g., lower alkyl esters) or as solvates (e.g., hydrates) to optimisethe activity and/or stability of the medicament.

[0109] Preferred medicaments are selected from albuterol, salmeterol,fluticasone propionate and beclomethasone dipropionate and salts orsolvates thereof, e.g., the sulphate of albuterol and the xinafoate ofsalmeterol.

[0110] Medicaments can also be delivered in combinations. Preferredformulations containing combinations of active ingredients containsalbutamol (e.g., as the free base or the sulphate salt) or salmeterol(e.g., as the xinafoate salt) or formoterol (eg as the fumarate salt) incombination with an antiinflammatory steroid such as a beclomethasoneester (e.g., the dipropionate) or a fluticasone ester (e.g., thepropionate) or budesonide. A particularly preferred combination is acombination of fluticasone propionate and salmeterol, or a salt thereof(particularly the xinafoate salt). A further combination of particularinterest is budesonide and formoterol (e.g. as the fumarate salt).

[0111] It may be appreciated that any of the parts of the medicamentcontainer used therewith which contact the medicament may be coated withmaterials such as fluoropolymer materials which reduce the tendency ofmedicament to adhere thereto. Suitable fluoropolymers includepolytetrafluoroethylene (PTFE) and fluoroethylene propylene (FEP). Anymovable parts may also have coatings applied thereto which enhance theirdesired movement characteristics. Frictional coatings may therefore beapplied to enhance frictional contact and lubricants used to reducefrictional contact as necessary.

[0112] It will be understood that the present disclosure is for thepurpose of illustration only and the invention extends to modifications,variations and improvements thereto.

[0113] The application of which this description and claims form partmay be used as a basis for priority in respect of any subsequentapplication. The claims of such subsequent application may be directedto any feature or combination of features described therein. They maytake the form of product, method or use claims and may include, by wayof example and without limitation, one or more of the following claims:

1. A container for a medicament powder formed from a material comprisinga desiccant.
 2. A container according to claim 1, wherein said containeris an medicament dispenser comprising a body defining a reservoir formedicament in powder form, and an outlet in communication with saidreservoir for release of medicament therefrom.
 3. A container accordingto claim 1, wherein the container is an medicament dispenser comprisinga body defining a chamber for receipt of a medicament carrier, and anoutlet in communication with said chamber for release of medicamenttherefrom.
 4. A container according to either of claims 2 or 3, whereinsaid body consists of said material comprising said desiccant.
 5. Acontainer according to either of claims 2 or 3, wherein said bodycomprises said material comprising said desiccant.
 6. A containeraccording to either of claims 2 or 3, wherein the material comprisingthe desiccant coats the body.
 7. A container according to either ofclaims 2 or 3, wherein the material comprising the desiccant isimpregnated throughout the body.
 8. A container according to either ofclaims 2 or 3, wherein the material comprising the desiccant lines thebody.
 9. A container according to claim 1, wherein the container is amedicament carrier.
 10. A container according to claim 9 or 3, whereinsaid medicament carrier is a capsule comprising a wall enclosing themedicament.
 11. A container according to claim 9 or 3, wherein themedicament carrier is a blister pack comprising a base sheet and a lid.12. A container according to any of claims 9 to 11, wherein themedicament carrier comprises a material comprising a desiccant.
 13. Acontainer according to any of claims 9 to 11, wherein the materialcomprising the desiccant coats said wall, or said base sheet, or saidlid of the medicament carrier.
 14. A container according to any ofclaims 9 to 11, wherein the material comprising the desiccantimpregnates the wall, or base sheet, or lid of the medicament carrier.15. A container according to any of claims 9 to 11, wherein the materialcomprising the desiccant lines the wall, or base sheet, or lid of themedicament carrier.
 16. A container according to any of claims 11 to 15,wherein a well containing desiccant surrounds individual pockets in saidblister packs.
 17. A container according to any of claims 11 to 16,wherein the blister pack comprises a laminate comprising a desiccant.18. A container according to any of the preceding claims, wherein thematerial comprising the desiccant is an organic polymeric plastic.
 19. Acontainer according to claim 18, wherein said organic polymeric plasticis a polyamide.
 20. A container according to any of the precedingclaims, wherein the desiccant is selected from the group consisting ofsilica gel, zeolite, alumina, bauxite, anhydrous calcium sulphate,activated bentonite clay, water-absorbing clay, molecular sieve and anymixtures thereof.
 21. A container according to any of claims 1 to 20additionally comprising a medicament in dry powder form.
 22. A containeraccording to claim 21, wherein said medicament is suitable for thetreatment of respiratory disorders.
 23. A container according to eitherof claims 21 or 22, wherein said medicament is salmeterol xinafoate. 24.A container according to either of claims 21 or 22, wherein saidmedicament is fluticasone propionate.
 25. A container according toeither of claims 21 or 22, wherein said medicament is a combination ofsalmeterol xinafoate and fluticasone propionate.
 26. A method ofreducing water ingress into a medicament powder comprising using acontainer for a medicament powder according to any of the precedingclaims.
 27. A package for storage of a container for a medicament powderformed from a material capable of controlling the ingress of moisturethereto or egress of moisture therefrom.
 28. A package according toclaim 27, wherein the material is capable of controlling the ingress oregress of moisture such that the moisture content within the package isessentially constant.
 29. A package according to either of claims 27 or28, wherein the material enables moisture transfer in one way only. 30.A package according to any of claims 27 to 29, wherein the materialenables moisture transfer to a set maximum or minimum level within thepackage.
 31. A package according to any of claims 27 to 29, wherein thematerial enables moisture transfer within a set maximum or minimumtransfer rate.
 32. A package according to any of claims 27 to 31,wherein said package is wrappable and sealable around the container toform an enclosed volume in which the container is disposed, therebycontrolling ingress or egress of moisture.
 33. A package according toclaim 32, additionally comprising a desiccant within the enclosedvolume.
 34. A package according to claim 33, wherein said desiccant isselected from the group consisting of silica gel, zeolite, alumina,bauxite, anhydrous calcium sulphate, activated bentonite clay,water-absorbing clay, molecular sieve and any mixtures thereof.
 35. Apackage according to any of claims 27 to 34 wherein the package includesat least one heat sealable layer and at least one layer of a metal foil.36. A package according to claim 35, wherein the metal comprising saidmetal foil is selected from the group consisting of aluminium, tin,iron, zinc and magnesium.
 37. A package according to claim 36, whereinthe package includes protective layers located on the outside of thepackage.
 38. A package according to claim 37, wherein said protectivelayer comprises a polyester film and said heat sealable layer comprisesan ionomer film.
 39. A method of storing a container for a medicamentpowder comprising providing a packaging material which is capable ofcontrolling the flow of water vapour; filling a container with amedicament powder; wrapping said container with said package material toform an enclosed volume in which said container is disposed therein; andsealing the package.
 40. A method of storing a container for amedicament powder according to claim 39, additionally comprisingproviding a desiccant within the enclosed volume.
 41. A method accordingto either of claims 39 or 40, wherein said sealing comprises sealingsaid packaging material using a method selected from the groupconsisting of heat sealing, ultrasonic welding, laser welding, adhesivesealing and heat stamping.
 42. A packaged container, comprising acontainer containing a medicament powder; and an overwrap packageenclosing said container and a desiccant; wherein said container andsaid desiccant are sealable within said overwrap.
 43. A packagedcontainer according to claim 42, wherein said container is formed from amaterial comprising a desiccant.
 44. A packaged powder medicamentdispenser comprising a medicament dispenser for a medicament powder; andan overwrap package enclosing said medicament dispenser and a desiccant,wherein said medicament dispenser and said desiccant are sealable withinsaid overwrap.
 45. A packaged powder medicament dispenser comprising anmedicament dispenser for a medicament powder; and an overwrap packageenclosing said medicament dispenser, wherein said overwrap comprisesdesiccant.
 46. A packaged powder medicament dispenser according toeither of claims 44 or 45, wherein said desiccant is selected from thegroup consisting of silica gel, zeolite, alumina, bauxite, anhydrouscalcium sulphate, activated bentonite clay, water-absorbing clay,molecular sieve, zinc chloride and any mixtures thereof.
 47. A containerfor a medicament powder formed from a material capable of controllingthe ingress of moisture thereto or egress of moisture therefrom.
 48. Acontainer according to claim 47, wherein the material is capable ofcontrolling the ingress or egress of moisture such that the moisturecontent within the package is essentially constant.
 49. A containeraccording to either of claims 47 or 48, wherein the material enablesmoisture transfer in one way only.
 50. A container according to any ofclaims 47 to 49, wherein the material enables moisture transfer to a setmaximum or minimum level within the package.
 51. A container accordingto any of claims 47 to 49, wherein the material enables moisturetransfer within a set maximum or minimum transfer rate.